Compound Limonene has been already disclosed by the State of Art and knowledge, its chemical name is Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (+)-(R), or 1-methyl-4-prop-1-en-2-yl-cyclohexene. Molecular Formula is C10H16, a molecular weight of 136.32, it is a liquid which do not in water but in ethanol. Limonene consist of three optics isomers, d-limonene, l-limonene and dl-limonene.
d-limonene's chemical name is (4R)-1-methyl-4-prop-1-en-2-ylcyclohexene. It consist in oils extracted from the citrus rind, limon, bergamot, dill and orange, etc. Its boiling point is 178° C., 61° C. (1.60 kPa), Density is 0.8411.
l-limonene is little in the orange oils, it can to form by chemical synthesis from other aroma compounds. It consist in oils extracted from Russia turps, and cajeput, etc. Its boiling point is 177.6-177.8° C., 61° C. (100.7 kPa), Density is 0.8422.
dl-limonene consist in oils extracted from Siberian pine needle, Lemongrass, and vanilla, etc. its boiling point is 178° C., 64.4° C. (2.0 kPa). Density is 0.8402.
Anyone of tree above is oily liquid. To distill have not chemical change in normal press, but it can itself easily be oxidised to complex compounds as oxygenates and polymer, etc. their flash point is 48° C.
Molecular biological studies of drug's action show that the chiral drugs present stereoselectivity in its drug absorption, transport, distribution, metabolism, excretion in the body, and binding thim with targets including absorption, enzymes and ion channels, etc. Therefore, both pairs of enantiomer often show different characteristics of pharmacology, toxicology and different pharmacokinetic properties. In many cases, between pairs of the enantiomer of compound both have significant differences in pharmacological activity, metabolic processes, metabolic rate, and toxicity in the organism.
However, it is common sense to at least one of isomer with same feature when racemic has some feature, so that, we can think that dl-Limonene some pharmacological effects of d-limonene. Respectively, this compound Limonene is obtained from the volatile oil of following plants or herbs, using the Fractionation method.
Rutaceae Lemon (Citrus limon (L.) Burm. f.) and its cultivar of the fresh mellow fruit, pericarp and leaf. Or, Rutaceae orange (Citrus reticulata Blanco) and its cultivar of the fresh mellow pericarp or dried mellow pericarp (It is called pericarpium Citri Reticulatae in traditional Chinese medicine), or dried little fruit or dried green pericarp (It Is called pericarpium Citri Reticulatae Viride in traditional Chinese medicine). Or, Sweet Orange (C. aurantium) of the fresh mellow fruit, pericarp and seed. Or, Sour Orange (Citrus aurantium) of the fresh mellow pericarp. Or, Sour Orange (Citrus aurantium) and its cultivar or Sweet Orange (C. aurantium) of the dried green pericarp (It Is called Fructus Aurantii lmmaturus in traditional Chinese medicine). Or, Wasp Orange (C. hystrix) of the fresh mellow fruit and pericarp. Or, Citrus Bergamia (C. bergamia) of the fresh mellow fruit and pericarp. Or, Rutaceae Fingered Citron (Citrus medica L. Var Sarcodactylis Swingle) of the fresh green pericarp or dried pericarp. Or, Umbelliferae Rhizoma seu Padix Notopterygii (Notopterygium incisum Ting ex H. T. chang) or wide blade Umbelliferae Rhizoma seu Padix Notopterygii (N. forbesii Boiss) of the root-stock and root. Or, Zingiberaceae Ginger (Zingiber officinale (Willd) Rosc.) of the fresh root-stock. Or, Perilla Leaf (Perilla frutescens (L.) Britt.) of the root. Or, Magnoliaceae Yulan (M. denudate Desr. [M. heptapeta (Buch.) Dandy; M. conspicua Salisb; M. yulan Desr.]) or Yulan in Wudang (M. sprengeri Pamp.) of the dried bud (It is called Flos Magnoliae in traditional Chinese medicine). Or, Herba Schizonepetae (Schizonepeta tenuifolia Briq) of the portion found above ground. Or, Umbelliferae North Radix Bupleuri (Bupleurum Chinense DC.) or narrow leaf (B. scorzonerifolium Willd (B. falcatum L. var. scorzonerifolium Ledeb.)) of the dried root (It is called Radix Bupleuri in traditional Chinese medicine). Or Japanese B. falcatum L. (B. scorzonerifolium willd var stenphyllum Nakai) of the dried root. Or, Labiatae Herba Menthae [Mentha haplocylyx Briq. (M. arvensis L. var haplocalyx Briq.) and Mentha haplocalyx Briq. (Var piperasoens (Malinvand) C. Y. Wu et H. W. Li (M. arvensis L. var piperascens Malinvaud.))] of the herb. Or, Saururaceae houttuynia cordata (Houttuynia cordata Thunb) of the herb (It is called Herba Houttuyniae in traditional Chinese medicine). Or, Asteraceae Flos Chrysanthemi Indici (Chrysanthemum indicum L.) of the capitulum. Or, Piperaeeae Piper kadsura (Piper kadsura (choisy) Ohwi and Piper walli chii (Miq) Hand-Mass) of the dried rattan (It is called Caulis Piper Kadsurae in traditional Chinese medicine). Or, Labiatae Glechoma hederacea (Glechoma longituba (Nakai) Kupr.) of the portion found above ground (It is called Herba Glechomae in traditional Chinese medicine). Or, Rutaceae Pericarpium Zanthoxyli (Zanthoxylum schinifolium Sieb. Et Zucc.), or Pricklyash Peel (Zanthoxylum bungeanum Maxim), or Zanthoxylum simulans (Z. simulans Hance) of the dried mellow pericarp. Or, Umbelliferae Fennel (Citrus aurantium L.) of the dried mellow fruit (It is called Fructus Foeniculi in traditional Chinese medicine). Or, Rutaceae Sour Orange (Citrus aurantium L.) and its cultivar of the crude fruit (It is called Fructus Aurantii in traditional Chinese medicine). Or, Umbelliferae Caraway (Carum carri L.) of the fruit (It is called Fructus cari carvi in traditional Chinese medicine). Or, Chenopodiaceae Herba Chenopodii (Chenopodium ambrosioides L.) of the herb. Or, Compositae Artemisia Vulgaris (Artemisia argyi Le vl. et Vant.) of the dried leaf. Or, Gramineae Cymbopogon distans (Cymbopogon Distans (Nees) A. Camus) of the herb. Or, Pinaceae White Bark Pine (Pinus bungeana Zucc.) of the cones (It is called Strobilus Pini Bungeanae in traditional Chinese medicine). Or, Ericaceae Rhododendron lutescens (Rhododendron anthopogonoides Maxim.) of the herb. Or, Erigeron Breviscapus (Erigeron breviscapus (Vant.)Hand.-Mazz) of the dried herb (It is called Herba Erigeronis Breviscapi in traditional Chinese medicine). Or, Compositae Artemisia Annua (Artemisia annua L.) of the herb (It is called Herba Artemisiae Annuae in traditional Chinese medicine). Or, Rutaceae Garden Rue (Ruta graveolens L.) of the herb (It is called Herba Rutae in traditional Chinese medicine). Or, Luraceae Litsea Cubeba (Litsea cubeba (Lour.) Pers.) of the dried mellow fruit (It is called Fructus Litseae in traditional Chinese medicine). Or, Magnoliaceae Chinese Anise (Illicium verum Hook. f.) of the dried mellow fruit. Or, Compositae Carpesium Abrotanoides (Carpesium abranoides L.) of the dried mellow fruit (It is called Fructus Carpesii in traditional Chinese medicine). Or, Labiatae Pogostemon cablin (Pogostemon cablin (Blanco) Benth.) and Agastache (Agastache rugosus (Fisch. et Mey.) O. Ktze) of the herb. Or, Cyperaceae Cyperus rotundas (Cyperus rotundus L.) of the root-stock. Or, Burseraceae Myrrh (Commiphora myrrha Engl.) of the Resins from bark. Or, Zingiberaceae Cardamomum (Amomum villosum Lour.) and Amomum xanthioides (A. villosum Lour. Var xanthioides T. L. Wu et Senjen) and Amomum longiligulare (A. longiligulare T. L. Wu) of the dried mellow fruit (It is called Fructus Amomi in traditional Chinese medicine). Or, Labiatae Perilla Leaf (Perilla frutescens(L.)Britt.) of the dried leaf. Or, Valerianaceae Valerian (Valerian officinalis L.) and wide blade Valerian (V. officinalis L. var. latifolia Miq) of the root and root-stock. Or, Leguminosae Alfalfa (Medicago Sadiva L.) or Medicago polymorpha (Medicago hispida Guertn) of the herb. Or, Rutaceae Acronychia (Acronychia pedunculata (L) Miq) or Powell's pedunculata (A. baueri) of the leaf. Or, Labiate Mosla Scabra (M. scabra(Thunb.)C. Y. Wu et H. W. Li) of the herb. Or, Rutaceae Lemon basil (Ocimum basilicum var. citriodorum) of the leaf.
Plant essential oils also produce a large number of by-product when wiping out terpene from oils and distilling or making synthetic camphor.
Limonene is mainly used for enamel, lacquer and a variety of solvents of oil-resin, resin wax, metal drier, and used in the manufacture of synthetic resins and synthetic rubber. Used in food, detergent and other household essence, they can still artificial preparation of citrus oils for oral such as the orange flavor essence of the formula.
U.S. Pat. No. 4,083,994 published that d-limonene can be used as the active component of choleretic drugs. In addition, the toxicity experiments published by U.S. Pat. No. 4,083,994 showed that d-limonene has extremely low toxicity. d-limonene's high biological safety are suitable for oral use. when administered d-limonene to rats by orally, LD50 for 6.0 g/kg.
The state of art and knowledge published that part of the pharmacokinetic data of d-limonene. d-limonene is absorbed rapidly after oral administration from the gastrointestinal, and it is distributed to all parts of the body, 75-95% of the absorbed drug will excreted by the urethra within 48 hours. limonene is excreted mostly by the urethra, about 60% of the all is eliminated in the urine within 24 hours, 5% is eliminated in the dejecta, and 2% is eliminated in the CO2 exhaled. Its primary metabolites are the Dihydrotestosterone acid Perilla and Perilla acid, convert from about 35% limonene of in plasma. After oral administration of limonene, Perilla acid methyl ester and Dihydrotestosterone Perilla acid methyl ester are measured in plasma, but there has 5% from initial limonene only. Another metabolite is limonene 1,2-diol, convert from about 18% limonene of the initial volume.
Diabetes is a complex disease characterized by hyperglycemia. The disease can be divided into two major subclasses: insulin-dependent diabetes mellitus (IDDM), also known as type I diabetes, and non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes. IDDM results from insulin deficiency caused by cell-mediated autoimmune destruction of pancreatic beta cells. (World Health Organization Study Group. Diabetes mellitus. WHO Tech. Rep. Ser. 844, 1994). Type 1 diabetes develops when the body's immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin that regulates blood glucose. Type 1 diabetes may account for 5% to 10% of all diagnosed cases of diabetes.
Type 2 diabetes may account for about 90% to 95% of all diagnosed cases of diabetes. It usually begins as insulin re-sistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce insulin. (U.S. Department of Health and Human Services, CDC, National Diabetes Fact Sheet, 2003).
Both IDDM and NIDDM can cause macrovascular, microvascular and neuropathy complications. Diabetes can affect many parts of the body and can lead to serious complications such as blindness, kidney damage, and lower-limb amputations.
In 2003, the Centers for Disease Control and Prevent (CDC) of China estimated about 40 million people have diabetes in China. European Union estimates that about 22.5 million people have type 2 diabetes in Europe in 2005. 20.8 million people have diabetes in the United States in 2005. Estimated cost of diabetes in the United States, 2002 Total (direct and indirect) for $132 billion, Direct medical costs for $92 billion, Indirect costs for $40 billion (disability, work loss, premature mortality). The World Health Organization (WHO) estimates that more than 180 million people worldwide have diabetes in 2005.
Current, major drugs of treatment of type 2 diabetes have some following:
1. Biguanides, its effective is low, and have biggish side-effect, often cause lactic acidosis if use for long-term.
2. Sulfonylureas, its side-effect is bigger, and often occur hypoglycemia if use for long-term, and islets of Langerhans may occur tire or crock up, secrete function of endogenesis insulin farther reduce, the drugs may secondary failure.
3. Glucosidase inhibitors, It delay absorb of glucose on small intestine only, and reduce postprandial blood glucose levels. It can not activate release of insulin, and also can not change fasting insulin and C-peptide concentration level.
4. Alone use insulin to treatment of type 2 diabetes, or use drugs type 1-3 above combining insulin, secrete function of endogenesis insulin will bankrupt, final result in insulin dependence. (WHO Study Group, WHO Technical Report Series 844, 1994)
All drugs above can not reduce blood glucose levels steadily. At the same time, the patient will need gradually increase the dosage of these drugs. United Kingdom prospective diabetes study indicate that all drugs can not stop sostenuto rise of fasting plasma glucose levels, indicating failure of islet cell function. (United Kingdom Prospective Diabetes Study Group, United Kingdom Prospective Diabetes Study, 1977-1992)
The current stability of the drug is difficult to control the disease process, diabetes, so there is no known case of the world, cured diseases, diabetes medication will be for life.
Present, Pharmaceutical companies and scientists are looking for newer versions of older agents, which may be more effective and have fewer side effects as well as entirely new agents with different mechanisms of actions.